Process for the production of a condensation products of a carboxylic acid

ABSTRACT

The invention provides a process for the production of a condensation product selected from the group consisting of an amide and an ester of a carboxylic acid from an organic compound selected from the group consisting of organic compounds carrying a hydroxyl group and organic compounds carrying an amine group and from a concentrated medium resulting from fermentation, said medium containing a salt of the acid, the salt being selected from the group consisting of a sodium salt, a calcium salt, and mixtures thereof and the medium being at a pH of at least the pKa of the acid, the process comprising reacting the medium with the organic compound and with CO 2 , whereby the condensation product and a salt selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate, and mixtures thereof are formed; and, separating the condensation product from the reaction mixture formed in the previous step.

The present invention relates to a process for the production of acondensation product of carboxylic acid from a concentrated mediumresulting from fermentation containing a salt of said acid. Morespecifically, the present invention is particularly useful as animportant step in the production of a low cost esters especially in theproduction of lactic acid and in the production of biodegradablepolylactic acid.

Carboxylic acids such as citric, lactic, succinic and malic acids can beproduced by the continuous or batch fermentation of sugars, or otherbiomass streams, such as: hydrolyzed starch. Production is productinhibited and slows with pH reduction reaching a point at which saidprocess is no longer practical. Product concentration in these solutionsis in most cases very low, below 1%, and the high energy requirements ofits concentration make the whole process uneconomical. In order toenhance fermentation, a base is added to maintain the pH at an optimallevel, in most cases at about or somewhat higher than the pKa of theacid. More concentrated medium resulting from fermentation is obtainedbut said medium contains the salt of the acid rather than the free acid.Since in most cases the free form of the acid is the final product ofinterest, the substantial cost of acidulation is added. In many casesaciduation is performed by adding a strong mineral acid that displacesthe carboxylic acid from the salt. Thus a base is consumed in thefermentation, a mineral acid in the acidulation and a salt is formed asan unwanted by-product. Lactic acid production, for example, uses acalcium base (mostly hydroxide) as the neutralizing agent. The mediumresulting from fermentation obtained, containing calcium lactate, istreated with sulfuric acid to precipitate calcium sulfate and liberatethe lactic acid. The latter is, however, left with most of theimpurities present in the medium resulting from fermentation andrequires additional operations for purification. Purification istypically performed by esterification in a reaction with an alkanol anddistillation of the ester. The purified ester can be used as such or behydrolysed to recover pure lactic acid and the alkanol.

Lactic acid has long been used as a food additive and in variouschemical and pharmaceutical applications. More recently, lactic acid hasbeen used in the making of biodegradable polymers both as a replacementfor present plastic materials as well as various new uses in whichbiodegradability is needed or desired. Accordingly, there is an everincreasing demand for lactic acid. The present invention aims at meetingthis demand by providing an efficient and low cost process for producinglactic acid esters or polyesters which avoids the consumption of basesand acids and substantially reduces, if not eliminates, the formation ofwaste salts.

Production of lactic acid is commonly carried out by fermentation of astrain of the bacterial genus Lactobacillus and more particularly by thespecies Lactobacillus delbrueckii or LactobacilIus acidophilus. Thefermentation substrate consists of carbohydrates together with suitablemineral and proteinaceous nutrients. Because the lactic acid producingmicro-organisms are inhibited in a strongly acidic environment, the pHof the fermentation broth must be kept above 5.0, and preferably withinthe rage of about 5.0 to 5.5. To maintain this pH level, suitablewater-soluble basic substances that are non-toxic to the acid producingmicro-organism, such as alkali metal or alkaline earth-metal carbonates,are commonly added to the fermentation broth. This results in theformation of a lactate solution rather than the desired lactic acidproduct. Acidulation is thus required.

Various sources of lactic acid may be used for production of polylacticacid biodegradable polymer. These sources include, as disclosed in U.S.Pat. No. 5,142,023, lactic acid in solutions with hydroxylic medium suchas water or other solvents, such as: low molecular weight alkanols andmixtures thereof. The source of lactic acid could also be an ester oflactic acid with a low molecular weight alkanol. The lactic acid sourceis first fed to an evaporator in which a portion of the water or solventor any condensation reaction by-product is removed and optionallyre-cycled. The evaporator thus concentrates the lactic acid causing somecondensation. Oligomers and low molecular weight polymers start to form.The concentrated lactic acid is next fed to a pre-polymer reactor inwhich low molecular weight polylactic polymer is formed. The pre-polymeris then converted to the lactide which is purified and fed to apolymerization system in which the product is formed.

The present invention aims at producing lactic acid esters or polyesters(oligomers) suitable for use as lactic acid sources (as they are orafter hydrolysis) in such a process.

Acidulation and esterification can be combined to one process asdisclosed by Cockrem and Johnson (PCT, WO 93/00440). A fermentationbroth containing ammonium lactate or another basic salt of lactic acidis acidified in the presence of an alcohol of 4-5 carbon atoms as adiluent using continuous addition of sulfuric acid or other strong acidand crystallizing to precipitate out some, or all, of the basic salt ofthe strong acid. This combined process, however, also consumes a baseand a strong acid and produces a low value by-product.

The present invention applies CO₂ as a displacing acid which issurprising as CO₂ is about 7 orders of magnitude weaker than sulfuricacid used by Cockrem and also much weaker than carboxylic acids. Thus,in the present invention CO₂ is a reagent and is used in stoichiometricquantities during the esterification process. One aim of the presentinvention is to produce a condensation product selected from the groupconsisting of an amide and an ester of a carboxylic acid without the useof a base and a strong acid and to minimize the production of salts asby-products. The term ester as used herein in reference to the presentinvention, unless specified otherwise, is intended to include diesters,lactones, oligoesters and polyesters.

The present invention provide s a process for the production of acondensation product selected from the group consisting of an amide andan ester of a carboxylic acid from an organic compound selected from thegroup consisting of organic compounds carrying a hydroxyl group andorganic compounds carrying an amine group and from a concentrated mediumresulting from fermentation, said medium containing a salt of said acid,said salt being selected from the group consisting of a sodium salt, acalcium salt and mixtures thereof and said medium being at a pH of atleast the pKa of said acid, said process comprising:

(a) reacting said medium with said organic compound and with CO₂,whereby said condensation product and a salt selected from the groupconsisting of sodium carbonate, sodium bicarbonate, calcium carbonate,calcium bicarbonate and mixtures thereof are formed; and,

(b) separating said condensation product from the reaction mixtureformed in step a.

Reacting carboxylic acids with organic compounds carrying a hydroxylgroup forms esters according to the equation:

RCOOH+R′OH═RCOOR′+H₂O

If any of the reagents or both of them are polyfunctional so that ahydroxyl group or a carboxylic group are present on the ester, thelatter could further react to form diester and higher esters. In asimilar way reacting of a carboxylic acid with organic compoundscarrying a primary or a secondary amine group forms amides, dimides orhigher amides according to the following equation:

RCOOH+R′NH₂═RCONHR′+H₂O

Both ester formation and amide formation are referred to in the generalterm: condensation reactions; esters and amides are referred to ascondensation products. Both reactions of carboxylic acids involve, inmost cases, water formation and are enhanced by lowering the watercontent in the reaction medium as well as by removing the by-productwater from the reaction medium. Low water content can be achieved byoperating in a solvent phase, using highly concentrated aqueoussolutions of the reagents and/or adding other components (soluble orinsoluble), which are highly hydrophilic and compete for the availablewater. Both reactions are usually conducted at elevated temperatures,preferably in the presence of a catalyst.

In most cases both the ester and the amide are more volatile than thecarboxylic acid forming them, which allows purification by distillation.In both cases, reacting the condensation product with water in a systemwith high water activity reverses the reaction. The condensation productis hydrolyzed reforming the carboxylic acid and the organic compoundcarrying the hydroxyl group or the organic compound carrying the aminegroup. Those could be separated to form a pure carboxylic acid and areagent that can be reused in the condensation reaction.

In those cases where another ester or amide is the desired product, thecarboxylic acid formed on the hydrolysis could be reacted again with asuitable alkanol or amine. Yet, in many cases the hydrolysis can beavoided. The condensation first product can be reacted with a hydroxylgroup carrying compound (R′OH) or an amine carrying compound (R′NH₂) todirectly form the desired product and to reform the reagent. Thus,RCOOR′ can be reacted with R″OH and RCONHR′ reacted with R″NH₂ accordingto the following equation:

RCOOR′+R″OH══RCOOR″+R′OH

OR

 RCONHR′+R″NH₂══RCONHR″+R′NH₂

where RCOOR″ or RCONHR″ are the desired product and R′OH or R′NH₂ can bereused in the first step. This reaction is driven forward by removal ofR′OH and RNH₂ from the reaction mixture. Furthermore, RCOOR′ can bereacted with R″NH₂ to form RCONHR″ and R′OH and RCONHR′ can be reactedwith R″OH to form RCOOR″ and R′NH₂.

In especially preferred embodiments of the present invention there isprovided a process for the production of an ester of a carboxylic acidfrom an organic compound carrying a hydroxyl group and from aconcentrated medium resulting from fermentation containing a salt ofsaid acid, said salt being selected from the group consisting of asodium salt, a calcium salt and mixtures thereof and said medium beingat a pH of at least the pKa of said acid, said process comprising:

(a) reacting said medium with said organic compound and with CO₂,whereby said ester and a salt selected from the group consisting ofsodium carbonate, sodium bicarbonate, calcium carbonate, calciumbicarbonate and mixtures thereof are formed; and,

(b) separating said ester from the reaction mixture.

Said process is useful in a low cost production of esters of carboxylicacids such as citric, lactic, succinic and malic. More specifically, thepresent invention is particularly useful as an important step inproduction of a low cost lactic acid and in the production of thebiodegradable polylactic acid.

Walkup et. al. (U.S. Pat. Nos. 5,071,754 and 5,252,473) disclose aprocess for forming lactic acid esters providing for base re-cycle andavoiding the consumption of a strong acid and the formation ofby-product salts.

Walkup uses ammonia as a base in fermentation and ammonium lactate isobtained. Alcohol is added to the ammonium lactate solution and furthercatalyzing amounts of gaseous CO₂ is applied to produce lactate esterwhich is separated and purified by distillation.

One of the important factors in the efforts to achieve a low-cost lacticacid is to recover and recycle the base. According to the Walkup U. S.patents, ibid. this is done by the distillation of the gaseous ammonia,but it is admitted (Column 8, Line 52) that recycling may not bejustified and that there are some difficulties in recovering the ammoniain a sufficiently pure form. There are some additional disadvantages inWalkups' processes. Ammonia tends to form amides with lactic and othercarboxylic acids at the temperatures and dehydrating conditions used inWalkup's patents. Furthermore, it is not convenient to establish asynthetic production with ammonia as it is a gas with a well-knownunpleasant smell. In contradistinction, it is suggested in the presentinvention to use sodium or calcium salt instead of the ammonium salt andthus carbonate or bicarbonate of sodium or calcium are formed and caneasily be separated, purified and further used in fermentation.Moreover, Walkup's process is comprised of two main steps. The firststep is converting the lactic acid salt (ammonium lactate) to lacticacid and NH₃, and the second step is the esterification of lactic acid.According to Walkup, the conversion rate is controlled by the first stepwhich has a low equilibrium constant. In the present invention thelactate salts are of bases much stronger than ammonia and thus the highconversion achieved by the process of the present invention issurprising.

Walkup uses CO₂ as a catalyst. This is clearly shown in his datasummarized in his FIG. 2. Substantial yields are obtained in the absenceof CO₂ under nitrogen atmosphere at 150° C. Pressurization with CO₂ atthe same temperature does increase yields, but in most cases by lessthan 20%. In the present invention CO₂ is a reagent and preferably isused in amounts of about or higher than equivalent to the carboxylicacid salt in the medium resulting from fermentation. In cleardistinction from Walkup the present invention is impractical withoutCO₂.

Walkup discloses (Column 8, Lines 15-21) that polymers are not formed inhis process. The present invention provides for the production ofpolyesters.

As stated, the present invention relates to a low cost process forproduction of esters. The invention is applicable for esters formed fromany combination of salts of hydroxycarboxylic, dicarboxylic andpolycarboxylic acids and alkanols, diols or polyols (organic compoundscarrying two or more hydroxyl groups). The term “carboxylic acid”includes also a hydroxy carboxylic acid, diacids and polyacids. Suitablecarboxylic acids are citric, lactic, succinic and malic acid. Thepresent description will be focused on lactic acid without limiting thescope of the invention.

The concentrated medium resulting from fermentation comprising sodium orcalcium salt of the carboxylic acid is at a pH close to or above the pKaof the acid. The organic compound carrying the hydroxyl group can belactic acid, glycolic acid or their sodium or calcium salts.

In the first step of the process according to the present invention,said medium resulting from fermentation and said hydroxyl group carryingorganic compound are reacted with CO₂ whereby the ester is formed andcarbonate or bicarbonate of sodium or calcium are formed. In the secondstage of said process the ester is separated from the reaction mixture.The reaction temperature is preferably from approximately 20° C. to 200°C. The reaction pressure is preferably 5 atmospheres to about 100atmospheres.

The process according to the invention may have an additional step ofhydrolyzing the separated ester to form high purity acid.

In a preferred embodiment a solvent is present in the reaction, saidsolvent being substantially immiscible in said medium resulting fromfermentation, and a good solvent of the ester formed. The ester formedfrom an acid salt and from said organic compound is less hydrophilicthan the acid salt forming it. As a result, it selectively fractionatesinto a solvent, if present in the system. This selective fractionationshifts the reaction equilibrium toward the product and improvesconversion. It also provides means of separating the product from thereaction mixture. This solvent should have low volatility in thereaction temperature and pressure. It should be substantially immisciblewith the concentrated medium resulting from fermentation in theseconditions. Ethers, aldehydes, ketones and other solvents, particularlythose used in the food industry are suitable.

In a particularly preferred embodiment, most of the ester is present inthe solvent phase and is recovered from that phase after it is separatedfrom the aqueous solution and from the bicarbonate or carbonate. Productseparation from the solvent can be performed in well known methods,including distillation, precipitation and addition of non-solvents. Itis particularly preferred to perform the separation by distillation ofthe product or the solvent. The boiling points of the product and thesolvent should differ by about 10° C. or more.

In a preferred embodiment the hydroxyl group carrying organic compound,particularly, an alkanol, has relatively low solubility in theconcentrated medium resulting from fermentation and, when used inexcess, forms a separate phase acting as a solvent for the product.Alkanols of three carbon atoms and more are suitable.

In a preferred embodiment, an esterification catalyst is used in thereaction. Strong acids are not desired as they may interfere withbicarbonate or carbonate production. Neutral catalysts such as aluminiumsulfate are preferred.

In another preferred embodiment, the catalyst is an enzyme. Proteases,esterases and lipases are examples of suitable enzymes.

Hydroxycarboxylic acid comprise both a hydroxyl and a carboxyl group andcan therefore act as both the acid source and hydroxyl source foresterification. Alkanol is not required as a reagent. Intermolecularreactions in concentrated medium resulting from fermentation containingsalts of hydroxycarboxylic acid need only CO₂ as a reagent to form thediester and the corresponding carbonate or bicarbonate. The diesterformed has a hydroxyl and a carboxyl group and can further react. It mayform an intramolecular esterification to lactone (lactide in the case oflactic acid) or react with more CO₂ and additional hydroxycarboxylicacid salt molecules to form oligomers and higher polyesters.

Ester formation from an acid and a hydroxyl carrying organic compoundform water as a by-product according to the equation:

RCOOH+ROH⇄RCOOR+H₂O

Water present in the system therefore drives the esterification backwardand should therefore be limited, in a preferred embodiment of theprocess, the medium resulting from fermentation used in the process isin concentration of about 40% w/w or higher. These concentrations arenot reached in fermentation in most cases and medium resulting fromfermentation should be concentrated by water evaporation. Otherpre-treatments may be helpful such as filtration, ultrafiltration andcarbon treatment.

In a preferred embodiment, water is removed from the system by theaddition of water absorbing agents or by distillation. Low molecularweight alkanols such as ethanol have a similar effect. If the hydroxylcarrying organic compound is a low molecular weight alkanol it can beused in an excess, driving the reaction forward also by binding water inthe system and reducing its activity.

Water is formed as a by-product in the process described in U.S. Pat.No. 5,071,754, and U.S. Pat. No. 5,252,473.

NH₄Lactate⇄NH₃+LacticAcid

LacticAcid+ROH⇄ROLactate+H₂O

Similarly water is formed in WO 93100440

2NH₄Lactate+2ROH+H₂SO₄=2 ROLactate+(NH₄)₂SO₄+2H₂O

The water formed adds to the water in the medium resulting fromfermentation and hinders esterification. An effort should be made forwater removal. In a clear distinction in the process of this invention,as CO₂ is used as a reagent rather than as a catalyst, water does notform on bicarbonate formation as can be seen from the following reactionscheme:

NaLactate+CO₂+ROH═ROLa+NaHCO₃

Ca(Lactate)₂+CO₂+2ROH=2ROLa+Ca(HCO₃)₂

or is formed in just half the equivalent amount if a carbonate is formedas follows:

Ca(Lactate)₂+CO₂+2ROH⇄2ROLa+CaCO₃+H₂O

Fermentative production of many carboxylic acids is product inhibitedand slows with pH reduction, reaching a point at which it is no longerpractical. A basic compound is added as a neutralizing agent to maintainthe pH at an optimal level, in most cases at about or somewhat higherthan pKa of the acid. As a result, the medium resulting fromfermentation contains mainly the salt of the acid rather than the freeacid. Bases such as bicarbonate, carbonate or hydroxide of sodium andcalcium are particularly suitable.

In a preferred embodiment of the process of the present invention thecarbonate or bicarbonate of calcium or sodium formed in the reaction isseparated, purified and used as a neutralizing agent in thefermentation. Sodium bicarbonate and particularly calcium carbonate havelow water solubility and precipitate out of the reaction mixture.Separation can be assisted by methods known in the art includingcooling, removal of the solvent, or, in the case of using calcium basesin fermentation, release of CO₂ pressure after product removal. Theseparated bicarbonate or carbonate are suitable for use as neutralizingagents in the fermentation as they are or after purification andtreatment. Calcium carbonate, for example, can be calcined to calciumoxide which, preferably after conversion to calcium hydroxide, is thepreferred neutralizing agent in many fermentation processes. Sodiumbicarbonate is easily converted to soluble sodium carbonate by heatingin water. The resulting solution or a part of it can be purified ifrequired, for example by carbon treatment.

While the invention will now be described in connection with certainpreferred embodiments in the following examples so that aspects thereofmay be more fully understood and appreciated, it is not intended tolimit the invention to these particular embodiments. On the contrary, itis intended to cover all alternatives, modifications and equivalents asmay be included within the scope of the invention as defined by theappended claims. Thus, the following examples which include preferredembodiments will serve to illustrate the practice of this invention, itbeing understood that the particulars shown are by way of example andfor purposes of illustrative discussion of preferred embodiments of thepresent invention only and are presented in the cause of providing whatis believed to be the most useful and readily understood description offormulation procedures as well as of the principles and conceptualaspects of the invention.

EXAMPLE 1

100 gr. of filtered, sodium lactate containing, medium resulting fromfermentation were concentrated from about 10% salt to about 50% saltthrough water evaporation. 75 gr. of ethanol was added and the mixturewas introduced into a pressure reactor. Gaseous CO₂ was added and wasobserved to be absorbed in the reaction mixture. More CO₂ was addeduntil the pressure stabilized at 40 atmospheres. The temperature waselevated to 100° C. and the reaction mixture was stirred for 5 hours.The pressure and temperature were then lowered and the vessel wasopened. The amount of sodium bicarbonate and ethyl lactate found, showthat a major part of the sodium lactate was converted to sodiumbicarbonate and ethyl lactate. The sodium bicarbonate is filtered andconverted to soluble sodium carbonate treated by active carbon and issuitable for use in fermentation.

EXAMPLE 1a—A Comparative Example

The experiment in example 1 was repeated using nitrogen as the gasinstead of CO₂. No substantial absorption was observed and bicarbonateand ethyl lactate were not detected.

EXAMPLE 2

The experiment in Example 1 was repeated with few changes. The mediumresulting from fermentation contained calcium lactate that wasconcentrated to 30%. The amount of ethanol was increased to 120 gr. andthe final CO₂ pressure was 30 atmospheres. Here again, high conversionswere found.

EXAMPLE 3

The experiment in Example 1 was repeated with two differences. Thesodium lactate concentration in the concentrated broth was elevated to80% and methyl isobutyl ketone was introduced instead of ethanol. Polylactic acid was found in the solvent phase at the end of the experiment.

EXAMPLE 4

The experiment in Example 3 was repeated with butyl amine instead ofmethyl isobutyl ketone and at 140° C. Butyl lactide amide was found atthe end of the reaction.

EXAMPLE 5

Filtered sodium lactate solution resulting from fermentation wasconcentrated to form 45 g. solution of 75% sodium lactate. This solutionwas introduced into a pressure vessel together with 75 g. butanol and0.016 San(II) ethyl hexanoic acid. Gaseous CO₂ was introduced and wasobserved to be adsorbed in the reaction mixture. More CO₂ was added toreach 21 atmospheres and the temperature was elevated to 145° C. whilestirring. After 3 hours, a sample of the upper phase was taken, thepressure and the temperature were lowered and the vessel was opened.Three phases were found: a large solid phase composed of sodiumbicarbonate, some aqueous phase and an organic phase. An HPLC analysisof this organic phase show that it contained about 0.3 mol/Kg. of butyllactate and about that concentration of lactic acid.

It will be evident to those skilled in the art that the invention is notlimited to the details of the foregoing illustrative examples and thatthe present invention may be embodied in other specific forms withoutdeparting from the essential attributes thereof, and it is thereforedesired that the present embodiments and examples be considered in allrespects as illustrative and not restrictive, reference being made tothe appended claims, rather than to the foregoing description, and allchanges which come within the meaning and range of equivalency of theclaims are therefore intended to be embraced therein.

What is claimed is:
 1. A process for the production of a condensationproduct selected from the group consisting of an amide and an ester of acarboxylic acid from an organic compound selected from the groupconsisting of organic compounds carrying a hydroxyl group and organiccompounds carrying an amine group and from a concentrated mediumresulting from fermentation, said medium containing a salt of said acid,said salt being selected from the group consisting of a sodium salt, acalcium salt and mixtures thereof and said medium being at a pH of atleast the pKa of said acid, said process comprising: (a) reacting saidmedium with said organic compound and with CO₂, said CO₂ functioning insaid reaction to displace the carboxylate anion from said sodium andcalcium carboxylic salts, whereby said condensation product and a saltselected from the group consisting of sodium carbonate, sodiumbicarbonate, calcium carbonate, calcium bicarbonate and mixtures thereofare formed; and, (b) separating said condensation product from thereaction mixture formed in step a.
 2. A process according to claim 1,for the production of an ester of a carboxylic acid from an organiccompound carrying a hydroxyl group and from a concentrated mediumresulting from fermentation containing a salt of said acid, said saltbeing selected from the group consisting of a sodium salt, a calciumsalt and mixtures thereof and said medium being at a pH of at least thepKa of said acid, said process comprising: (a) reacting said medium withsaid organic compound and with CO₂, whereby said ester and a saltselected from the group consisting of sodium carbonate, sodiumbicarbonate, calcium carbonate, calcium bicarbonate and mixtures thereofare formed; and, (b) separating said ester from the reaction mixture. 3.The process of claim 1, wherein said organic compound is selected fromthe group consisting of alkanols, hydroxy carboxylic acids and saltsthereof.
 4. The process of claim 1, wherein the reaction is carried outat a temperature of between about 20° C. and 200° C.
 5. The process ofclaim 1, wherein the reaction is carried out at a pressure of about 5atmospheres to about 100 atmospheres.
 6. The process of claim 3, whereinsaid alkanol is selected from the group consisting of methanol, ethanol,propanol, isopropanol, butanol and isobutanol.
 7. The process of claim1, wherein said carboxylic acid is a hydroxy carboxylic acid.
 8. Theprocess of claim 1, wherein said organic compound is selected from thegroup consisting of lactic acid, glycolic acid and salts thereof.
 9. Theprocess of claim 1, wherein said carboxylic acid is selected from thegroup consisting of lactic acid, citric acid, malic acid and succinicacid.
 10. The process of claim 9, wherein said carboxylic acid is lacticacid.
 11. The process of claim 2, wherein said carboxylic acid is lacticacid and said ester is a lactic acid ester.
 12. The process of claim 11,wherein said lactic acid ester is a product of the reaction of at leasttwo lactic acid molecules.
 13. The process of claim 12, wherein saidester is selected from the group consisting of lactide, lactoyl lactate,lactic acid oligomers and polylactic acid.
 14. The process of claim 2,wherein said organic compound is a lactic acid salt, said salt beingselected from the group consisting of the sodium salt, the calcium saltand mixtures thereof.
 15. The process of claim 1, wherein the pH of saidfermentation is maintained by the introduction of a neutralizing agentselected from the group consisting of sodium carbonate, sodiumbicarbonate, calcium carbonate, calcium bicarbonate, sodium hydroxide,calcium hydroxide and mixtures thereof.
 16. The process of claim 15,wherein said salt formed in step (a) is separated and used as aneutralizing agent in said fermentation.
 17. The process of claim 1,wherein said salt precipitates in step (a).
 18. The process of claim 2,further comprising hydrolyzing the separated ester to form high-purityacid.
 19. The process of claim 2, further comprising converting saidester to polylactic acid.
 20. The process of claim 1, further comprisingwater removal.
 21. The process of claim 1, wherein a condensationcatalyst is used in the reaction.
 22. The process of claim 21, whereinsaid catalyst is an enzyme.
 23. The process of claim 2, wherein at leastone solvent is present in the reaction, said solvent being substantiallyimmiscible in said medium resulting from fermentation and being a goodsolvent for the ester formed.
 24. The process of claim 23, wherein saidsolvent is said organic compound when present in above-stoichiometricamounts.
 25. The process of claim 23, wherein said ester is recoveredfrom a phase formed by said solvent.
 26. The process of claim 25,wherein said ester is recovered from said solvent phase by distillation.27. The process of claim 1, wherein the concentration of the salt in themedium resulting from fermentation is at least 40% w/w.